Akaike T
Department of Microbiology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
Rev Med Virol. 2001 Mar-Apr;11(2):87-101. doi: 10.1002/rmv.303.
Oxygen radicals and nitric oxide (NO) are generated in excess in a diverse array of microbial infections. Emerging concepts in free radical biology are now shedding light on the pathogenesis of various diseases. Free-radical induced pathogenicity in virus infections is of great importance, because evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. Although oxygen radicals and NO have an antimicrobial effect on bacteria and protozoa, they have opposing effects in virus infections such as influenza virus pneumonia and several other neurotropic virus infections. A high output of NO from inducible NO synthase, occurring in a variety of virus infections, produces highly reactive nitrogen oxide species, such as peroxynitrite, via interaction with oxygen radicals and reactive oxygen intermediates. The production of these various reactive species confers the diverse biological functions of NO. The reactive nitrogen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules. The unique biological properties of free radicals are further illustrated by recent evidence showing accelerated viral mutation by NO-induced oxidative stress. NO appears to affect a host's immune response, with immunopathological consequences. For example, NO is reported to suppress type 1 helper T cell-dependent immune responses during infections, leading to type 2 helper T cell-biased immunological host responses. NO-induced immunosuppression may thus contribute to the pathogenesis of virus infections and help expansion of quasispecies population of viral pathogens. This review describes the pathophysiological roles of free radicals in the pathogenesis of viral disease and in viral mutation as related to both nonspecific inflammatory responses and immunological host reactions modulated by NO.
在多种微生物感染中，氧自由基和一氧化氮（NO）会过量产生。自由基生物学领域的新观点正在为各种疾病的发病机制提供新的线索。自由基诱导的病毒感染致病性非常重要，因为有证据表明，NO和超氧阴离子等氧自由基是各种传染病发病机制中的关键分子。尽管氧自由基和NO对细菌和原生动物具有抗菌作用，但它们在流感病毒肺炎等病毒感染以及其他几种嗜神经病毒感染中却具有相反的作用。在多种病毒感染中，诱导型NO合酶产生的大量NO通过与氧自由基和活性氧中间体相互作用，产生高反应性氮氧化物，如过氧亚硝酸盐。这些各种反应性物种的产生赋予了NO多样的生物学功能。活性氮物种通过氧化和硝化各种生物分子导致氧化组织损伤和诱变。最近的证据表明NO诱导的氧化应激会加速病毒突变，这进一步说明了自由基独特的生物学特性。NO似乎会影响宿主的免疫反应，并产生免疫病理后果。例如，据报道，NO在感染期间会抑制1型辅助性T细胞依赖性免疫反应，导致偏向2型辅助性T细胞的免疫宿主反应。因此，NO诱导的免疫抑制可能有助于病毒感染的发病机制，并有助于病毒病原体准种群体的扩增。这篇综述描述了自由基在病毒性疾病发病机制以及与非特异性炎症反应和由NO调节的免疫宿主反应相关的病毒突变中的病理生理作用。
